1. Technical Field of the Invention
The present invention relates to a class of derivatives of 3-phenyl acrylic acid that are activators of receptors of the Peroxisome Proliferator-Activated Receptor type, of subtype γ (PPARγ), as novel and useful industrial compounds. It also relates to their method of preparation and their formulation into pharmaceutical compositions useful in human or veterinary medicine, or in cosmetic compositions.
2. Description of Background and/or Related and/or Prior Art
The activity of the PPAR type receptors has been the subject of numerous studies. One example is the publication “Differential Expression of Peroxisome Proliferator-Activated Receptor Subtypes during the Differentiation of Human Keratinocytes”, Michel Rivier et al., J. Invest. Dermatol., 111, 1998, p 1116-1121, which lists a large number of bibliographical references concerning the PPAR type receptors. Another example is the report “The PPARs: From orphan receptors to Drug Discovery”, Timothy M. Willson, Peter J. Brown, Daniel D. Sternbach, and Brad R. Henke, J. Med. Chem., 2000, Vol. 43, p. 527-550.
The PPARs activate transcription by binding to elements of DNA sequences, known as the peroxisome proliferator response elements (PPRE), in the form of a heterodimer with the retinoid X receptors (known as RXRs).
Three subtypes of human PPARs have been identified and described: PPARα, PPARγ and PPARδ (or NUC1).
PPARα is mainly expressed in the liver whereas PPARδ is ubiquitous.
Of the three subtypes, PPARγ has received the most study. All of the references suggest a critical role of the PPARγ in regulation of the differentiation of adipocytes, where it is strongly expressed. It also plays a key role in systemic lipid homeostasis.
It was notably described in international application WO 96/33724 that selective compounds of the PPARγ, such as a prostaglandin-J2 or -D2, are potential actives for the treatment of obesity and diabetes.
Moreover, the assignee hereof has already described in WO 02/12210, WO 03/055867 and WO 2006/018326 the formulation of diaromatic compounds that are activators of the type PPARγ receptors into pharmaceutical compositions, such compositions being useful for the treatment of skin disorders linked to an abnormality of differentiation of the epidermal cells.
Nevertheless, need still exists for novel compounds that are activators of the type PPARγ receptors and display advantageous pharmaceutical properties.